Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The neighborhood matters: Packard Center scientists show cell environment is important in ALS

06.10.2003


In amyotrophic lateral sclerosis (ALS), neighborhood may be everything, if a new study in mouse models of the disease holds true for patients.



ALS, or Lou Gehrig’s disease, brings about a gradual death of the motor neurons that activate muscles. Paralysis follows. But according to work described today in the journal Science, the cells that are next to motor neurons -- but aren’t themselves nerve cells -- can play a major role in advancing or limiting the disease.

"What we’ve been given is a new principle for extending survival or, perhaps, overcoming ALS, based on how many healthy cells surround an ailing motor nerve cell," says Don Cleveland, Ph.D., a scientist with The Packard Center for ALS Research at Johns Hopkins and, with Larry Goldstein, Ph.D., co-leader of the research team. "All this has great implications for stem cell therapy," he adds. "We now believe delivery of normal, non-neuronal cells to spinal cords could be completely protective, even without replacement of a single motor neuron."


In a series of experiments, the team measured the effect of having different proportions of healthy cells to at-risk cells in mice, clocking their survival time. Normally, the scientists work with standard animal models of ALS. Those mice or rats carry a mutant human gene -- called SOD1 -- that triggers a rare, inherited form of the disease in people. In these models, every cell carries a mutant SOD1 gene. The animals typically slip into death by the time they’re six to eight months of age.

But in this study, the researchers used chimeric animals -- mice engineered to be a mix of normal cells, also called wild type, and cells containing the mutant SOD1 gene. They tagged the cells with molecular flags to make it clear which were which. The percent of wild-type cells in the animals’ spinal cords ranged from 5 to 90 percent.

Having wild type cells mixed in had the effect of extending mouse survival from one to eight months, depending on the number of cells and type of SOD1 mutation. In a second group of chimeric mice, brought about by a different technique and with a different type of tracer, the animals survived disease-free until sacrificed for study at an age at least twice the age at which typical SOD1 animal models die.

Even though further study showed that as high as three-fourths of the motor neurons in the animals’ spinal cords carried the mutant gene, all the motor neurons remained amazingly healthy, apparently from having healthy non-neuronal cells in the neighborhood. This was especially true of the second batch of mice, which had no microscopic evidence of disease.

"It’s really striking," says Cleveland, "to see what a small number of normal cells effectively eliminated damage to motor neurons from the ALS-causing genetic error."

The opposite effect also appeared: mice with normal motor neurons but with surrounding cells carrying an SOD1 mutation showed early signs of disease. Normal neurons, then, can apparently acquire something toxic from at-risk non-neuronal neighboring cells.

"So we’re seeing a real-life metaphor here," says Cleveland. "Living in a bad environment can damage good cells. And more important, restoring a better environment to ’bad’ neurons by surrounding them with healthy neighbors can significantly lessen toxic effects. In some cases, having normal cells completely stops motor neuron death."

Research conducted by Center scientist and team member Jean-Pierre Julien, Ph.D., at Laval University in Quebec was a key contribution to the results. Researchers Cleveland and Goldstein are both at the University of California, San Diego, where Cleveland heads the Laboratory of Cell Biology at the Ludwig Institute for Cancer Research.

The research was funded by the Packard Center for ALS Research at Johns Hopkins, Project ALS, The ALS Association, the U.S. National Institutes of Health, the Canadian Institutes of Health Research, The Angel Fund for ALS Research and the U.S. Veterans Administration.

Headquartered in Baltimore, the Robert Packard Center for ALS Research at Johns Hopkins is a collaboration of scientists worldwide who are working aggressively to develop new treatments and a cure for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The Center is the only institution of its kind dedicated solely to the disease. Its research is meant to translate from the laboratory bench to the clinic in record time.

Joanna Downer | EurekAlert!
Further information:
http://www.hopkinsmedicine.org/

More articles from Health and Medicine:

nachricht Dengue takes low and slow approach to replication
12.01.2018 | Duke University

nachricht Fast food makes the immune system more aggressive in the long term
12.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

Im Focus: Autoimmune Reaction Successfully Halted in Early Stage Islet Autoimmunity

Scientists at Helmholtz Zentrum München have discovered a mechanism that amplifies the autoimmune reaction in an early stage of pancreatic islet autoimmunity prior to the progression to clinical type 1 diabetes. If the researchers blocked the corresponding molecules, the immune system was significantly less active. The study was conducted under the auspices of the German Center for Diabetes Research (DZD) and was published in the journal ‘Science Translational Medicine’.

Type 1 diabetes is the most common metabolic disease in childhood and adolescence. In this disease, the body's own immune system attacks and destroys the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fachtagung analytica conference 2018

15.01.2018 | Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

 
Latest News

Black hole spin cranks-up radio volume

15.01.2018 | Physics and Astronomy

A matter of mobility: multidisciplinary paper suggests new strategy for drug discovery

15.01.2018 | Life Sciences

New method to map miniature brain circuits

15.01.2018 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>